Indoleamine dioxygenase (IDO) degrades the indole moiety of tryptophan and initiates the production of neuroactive and immunoregulatory metabolites, collectively known as kynurenines. The functional expression of IDO by dendritic cells has emerged in recent years as a major mechanism of peripheral tolerance. IDO contributes to maternal tolerance in pregnancy, control of allograft rejection, and protection against autoimmunity, inflammatory pathology and allergy. IDO expression also serves a physiological mechanism by which malignancies induce immune tolerance (Uyttenhove et al. 2004; Mellor et al. 2004; Munn et al. 2004). The wide spectrum of physiopathological conditions in which IDO appears at work suggests that this suppressive system is frequently involved in physiological down regulation of T cell responses and resulting inflammatory responses. There are a number of known substances that induces IDO, wherein said compounds have different mechanisms of action. Examples of classes of such IDO inducers, having different mechanisms of action, are among others cytidine analogues, histone deacetylase inhibitors, vitamin D3 analogues, interferons, toll like receptor ligands, gonadotropine receptor signalling hormones, prostaglandine E2 analogues, IDO stabilisers, soluble CTLA4 conjugates, and glycocorticoids.
However, many of these substances increase the amount of IDO to levels which are too low to be suitable in pharmaceutical composition, and will thus require, to induce effective IDO levels, high doses that are not suitable for reasons of toxicology, compliance or costs. Therefore there is a need to develop new pharmaceutical compositions that, at suitable dose levels, could increase IDO to levels that are sufficient and therapeutically useful in the treatment of different autoimmune disorders and in the prevention of transplant rejections.